The invention relates generally to the field of hyaluronic acid and hyaluronate salts.
Hyaluronic acid (HA) is a member of a class of polymers known as glycosaminoglycans. HA is a long chain linear polysaccharide and is available in the form of a sodium salt which has the molecular formula of (C14H2ONNaO11)n where n can vary according to the source, isolation procedure, and method of determination. Molecular weights of up to 14,000,000 have been reported.
HA and its salt derivative can be isolated from many sources including nearly all connective matrices of vertebrate organisms. Additionally, HA is also a capsular component of bacteria such as Streptococci (Kendall et al, 1937, Biochem. Biophys. Acta, 279, 401–405) and some Bacilli (U.S. Patent Application Publication No. 2003/0175902).
HA is non-immunogenic and therefore has a wide array of applications in medicine, particularly in purified and sterilized forms. HA having a high molecular weight (>about 1 million) has been found to be particularly useful owing, at least in part, to its viscoelastic properties. The HA which is at present commercially available is generally obtained from avian sources such as rooster combs. This material is difficult to process, and repeated and complex purification procedures are needed. A suitable process is described in U.S. Pat. No. 4,141,973, for example. HA is often expensive for these reasons.
Existing commercial technologies to produce HA rely on one of several methods. Connective tissues, such as the combs of roosters, human umbilical cords or other known HA sources can be processed to yield HA. Alternately, the material can be produced through a fermentation process in which it is removed from the capsule surrounding Streptococci or other bacteria. Most known methods rely on the use of solvents such as chloroform, ethanol and acetone.
A need exists for a commercially feasible way to make large quantities of HA and HA salts (i.e., hyaluronates) in an economical manner. The present invention satisfies this need.